Lee Min-Woo, Odegaard Justin I, Mukundan Lata, Qiu Yifu, Molofsky Ari B, Nussbaum Jesse C, Yun Karen, Locksley Richard M, Chawla Ajay
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-9001, USA.
Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143-0795, USA.
Cell. 2015 Jan 15;160(1-2):74-87. doi: 10.1016/j.cell.2014.12.011. Epub 2014 Dec 24.
Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2- and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα(+) APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PAPERCLIP:
2型固有淋巴细胞（ILC2s）是2型细胞因子白细胞介素（IL）-5和-13的固有来源，参与维持组织稳态。尽管2型免疫对于介导对环境寒冷的代谢适应至关重要，但ILC2s在米色或棕色脂肪发育中的功能仍不清楚。我们在此报告，IL-33激活ILC2s足以促进处于热中性状态小鼠的功能性米色脂肪生长。从机制上讲，ILC2激活导致双潜能脂肪细胞前体（APs）增殖，并使其随后定向分化为米色脂肪谱系。功能缺失和功能获得研究表明，ILC2和嗜酸性粒细胞衍生的2型细胞因子通过PDGFRα(+) APs中的IL-4Rα刺激信号传导，以促进米色脂肪生成。总之，我们的结果突出了ILC2s和2型细胞因子在调节脂肪细胞前体数量和命运以及由此调节脂肪组织稳态中的关键作用。回形针：
